التفاصيل البيبلوغرافية
| العنوان: |
N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer's disease. |
| المؤلفون: |
Lee, Ju Youn, Han, Seung Hoon, Park, Min Hee, Song, Im-Sook, Choi, Min-Koo, Yu, Eunsoo, Park, Cheol-Min, Kim, Hee-Jin, Kim, Seung Hyun, Schuchman, Edward H., Jin, Hee Kyung, Bae, Jae-sung |
| المصدر: |
Nature Communications; 5/12/2020, Vol. 11 Issue 1, p1-19, 19p |
| مصطلحات موضوعية: |
MICROGLIA, ALZHEIMER'S disease, SPHINGOSINE kinase, PHAGOCYTOSIS, ACETYLCOENZYME A, ACETYLTRANSFERASES |
| مستخلص: |
Sphingosine kinase1 (SphK1) is an acetyl-CoA dependent acetyltransferase which acts on cyclooxygenase2 (COX2) in neurons in a model of Alzheimer's disease (AD). However, the mechanism underlying this activity was unexplored. Here we show that N-acetyl sphingosine (N-AS) is first generated by acetyl-CoA and sphingosine through SphK1. N-AS then acetylates serine 565 (S565) of COX2, and the N-AS-acetylated COX2 induces the production of specialized pro-resolving mediators (SPMs). In a mouse model of AD, microglia show a reduction in N-AS generation, leading to decreased acetyl-S565 COX2 and SPM production. Treatment with N-AS increases acetylated COX2 and N-AS-triggered SPMs in microglia of AD mice, leading to resolution of neuroinflammation, an increase in microglial phagocytosis, and improved memory. Taken together, these results identify a role of N-AS in the dysfunction of microglia in AD. Neuronal sphingosine kinase 1 (SphK1) acetylates COX2 which is needed for microglial phagocytosis activity, and release of pro-resolving mediators (SPMs) from neurons. Here the authors examine how SphK1-mediates COX2 acetylation, and how this leads to increased secretion of SPMs from neurons in the context of Alzheimer's disease models. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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